CN109453425B - 一种抗感染促进成骨的钛合金植入物及其制备方法 - Google Patents
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Abstract
本发明公开了一种抗感染促进成骨的钛合金植入物及其制备方法,该方法包含:步骤1,制备钛合金植入物本体;步骤2,对钛合金植入物本体表面进行碱热处理,并进行多巴胺活化;步骤3,进行HA嫁接,并再次进行多巴胺活化;步骤4,在室温环境下,将经步骤3处理的钛合金植入物本体浸泡在1~4mM硝酸银溶液中0.5~8小时,取出,晾干,再采用紫外光照射0.5~2小时,还原得到纳米Ag粒子层;步骤5,将经步骤4处理的钛合金植入物本体浸泡在1~4 mg/ml的壳聚糖中30s~5min,并进行干燥,完成载HA/Ag/Cs涂层钛合金植入物的制备。相较采用钛合金植入物,本发明制备的载HA/Ag/Cs涂层钛合金植入物具有优异的抗菌性能,并能够促进成骨与骨‑假体界面整合。
Description
技术领域
本发明涉及一种医用植入物,具体涉及一种抗感染促进成骨的钛合金植入物。
背景技术
钛及其合金具有良好的力学性能与生物相容性,是目前应用最为广泛的骨科植入物材料。
但是,钛合金材料植入人体后,相比正常人体组织,其表面缺乏血液供应,有利于细菌生长、粘附,引发感染。感染是骨科植入物术后灾难性的并发症,是植入物失败的主要原因之一。据报道,人工关节置换术后假体周围感染的概率为1-3%,利用髓内钉治疗开放性股骨或胫骨骨折的感染率则高达5%-10%。
因此,亟需制备具有良好抗感染性能的骨科植入物材料。
发明内容
本发明的目的是如何避免钛合金植入物引发的感染。
为了达到上述目的,本发明提供了一种抗感染促进成骨的钛合金植入物的制备方法,该方法包含:
步骤1,制备钛合金植入物本体;
步骤2,对钛合金植入物本体表面进行碱热处理,并进行多巴胺活化;
步骤3,进行HA嫁接,并再次进行多巴胺活化;
步骤4,在室温环境下,将经步骤3处理的钛合金植入物本体浸泡在1~4mM硝酸银溶液中0.5~8小时,取出,晾干,再采用紫外光照射0.5~2小时,还原得到纳米Ag粒子层;
步骤5,将经步骤4处理的钛合金植入物本体浸泡在1~4mg/ml的壳聚糖中30s~5min,并进行干燥,完成载HA/Ag/Cs涂层钛合金植入物的制备。
较佳地,所述的碱热处理是指,加热状态下,采用碱处理钛合金植入物。
较佳地,所述的碱热处理是指,水热釜中采用4M KOH,80℃,90min处理钛合金植入物。
较佳地,所述的多巴胺活化是指,将钛合金植入物置于多巴胺溶液中浸泡。
较佳地,所述的多巴胺活化是指,将钛合金植入物置于2mg/mL多巴胺溶液中浸泡24h。
较佳地,所述的HA嫁接是指,通过在包含HA的溶液中浸泡,在钛合金植入物的表面接枝HA,以使得钛合金植入物上布满HA。
较佳地,所述的HA嫁接是指,将钛合金植入物浸泡1倍模拟体液中接枝HA,并置于37℃恒温箱中,每三天换一次液,浸泡14天。
较佳地,采用3D打印制备钛合金植入物本体
本发明在HA嫁接后,再次进行多巴胺活化,可以利用多巴胺活化进一步减少银离子的释放。由于银离子细胞毒性存在剂量依赖,减少释放可减少细胞毒性,增加生物安全性。
本发明还提供了一种抗感染促进成骨的钛合金植入物,其包含:钛合金植入物本体,及,覆盖在该钛合金植入物本体上的HA/Ag/Cs涂层。
相较采用钛合金植入物,本发明提供的载HA/Ag/Cs涂层钛合金植入物具有优异的抗菌性能,并能够促进成骨与骨-假体界面整合。
附图说明
图1为本发明的抗感染促进成骨的钛合金植入物(载HA/Ag/Cs涂层钛棒)与钛棒分别植入大鼠股骨髓内4周后的对比图(X射线图)。
图2为本发明的抗感染促进成骨的钛合金植入物(载HA/Ag/Cs涂层钛棒)与钛棒分别植入大鼠股骨髓内12周后测得的假体与骨接触率柱状图。
具体实施方式
以下结合附图和实施例对本发明的技术方案做进一步的说明。
本发明还提供了一种抗感染促进成骨的钛合金植入物的制备方法,该方法包含:
步骤1,采用钛合金植入物或3D打印钛合金植入物本体;
步骤2,对钛合金植入物本体表面进行碱热处理,并进行多巴胺活化;所述的碱热处理是指在水热釜中用4M KOH,80℃,90min处理钛合金植入物;所述多巴胺活化是指将经碱热处理的钛合金植入物置于2mg/mL多巴胺溶液中浸泡24h;
步骤3,进行HA(hydroxyapatite,羟基磷灰石)嫁接,以在植入物上布满HA,并再次进行多巴胺活化;所述的HA嫁接是指,将植入物浸泡1倍模拟体液中接枝HA,并置于37℃恒温箱中,每三天换一次液,浸泡14天;
步骤4,在室温环境下,将经步骤3处理的钛合金植入物本体浸泡在1mM硝酸银溶液中6小时,取出,晾干,再采用紫外光照射1小时,还原得到纳米Ag粒子;
步骤5,将经步骤4处理的钛合金植入物本体浸泡在2mg/ml的壳聚糖(chitosan,CS)中2小时,并进行干燥,完成载HA/Ag/Cs涂层钛合金植入物的制备。
所述的载HA/Ag/Cs涂层钛合金植入物包含:钛合金植入物本体,及,覆盖在该钛合金植入物本体上的HA/Ag/Cs涂层。
所述的多巴胺能在钛合金表面形成聚多巴胺涂层,聚多巴胺涂层具有粘性,可以将HA等黏附在钛合金表面。
所述的壳聚糖(chitosan,CS)负责提高钛合金表面活性,促进成骨,加速骨-植入物界面整合。
所述的纳米Ag涂层具有良好的抗菌性能,可以预防细菌在材料表面黏附、生长。而且,由于HA与Cs的存在,多巴胺和壳聚糖的双重鳌和作用,可进一步减少银离子释放,增加载HA/Ag/CS涂层钛合金的生物活性与生物安全性,促进成骨与骨-植入物界面整合。
动物模型1:大鼠股骨髓内钉感染预防模型。将金黄色葡萄球菌污染的钛合金髓内钉(钛棒)与载HA/Ag/Cs涂层钛合金髓内钉(载HA/Ag/Cs涂层钛棒)植入大鼠股骨。通过与无涂层钛棒组对照,观察载HA/Ag/Cs涂层钛合金植入物的抗感染性能。实验组与对照组均采用10周龄健康大鼠。
结果显示,载HA/Ag/Cs涂层钛合金植入物较钛合金植入物具有明显的抗感染作用,植入4周后,X线显示钛合金植入物周围具有明显感染征象,而载HA/Ag/Cs涂层钛合金植入物组无明显感染表现,如图1所示。
此外,我们建立了钛合金植入骨整合动物模型。
动物模型2:钛合金植入骨整合动物模型,将钛合金植入物植入大鼠股骨建立非感染模型,通过与无涂层组对照,观察HA/Ag/Cs涂层钛合金植入物的骨整合性能。实验组与对照组,10周龄,健康大鼠。
结果显示,植入12周后,载HA/Ag/Cs涂层钛合金植入物与骨接触率高于钛合金植入物,提示载HA/Ag/Cs涂层钛合金植入物具有更好的促成骨与骨整合性能,如图2所示。
综上所述,相较采用钛合金植入物,本发明制备的载HA/Ag/Cs涂层钛合金植入物具有优异的抗菌性能,并能够促进成骨与骨-假体界面整合。
尽管本发明的内容已经通过上述优选实施例作了详细介绍,但应当认识到上述的描述不应被认为是对本发明的限制。在本领域技术人员阅读了上述内容后,对于本发明的多种修改和替代都将是显而易见的。因此,本发明的保护范围应由所附的权利要求来限定。
Claims (7)
1.一种抗感染促进成骨的钛合金植入物的制备方法,其特征在于,该方法包含:
步骤1,制备钛合金植入物本体;
步骤2,对钛合金植入物本体表面进行碱热处理,并进行多巴胺活化;所述的多巴胺活化是指,将钛合金植入物本体置于多巴胺溶液中浸泡;
步骤3,进行HA嫁接,并再次进行多巴胺活化;所述的HA嫁接是指,通过在包含HA的溶液中浸泡,在钛合金植入物本体的表面接枝HA,以使得钛合金植入物本体上布满HA;
步骤4,在室温环境下,将经步骤3处理的钛合金植入物本体浸泡在1~4mM硝酸银溶液中0.5~8小时,取出,晾干,再采用紫外光照射0.5~2小时,还原得到纳米Ag粒子层;
步骤5,将经步骤4处理的钛合金植入物本体浸泡在1~4 mg/ml的壳聚糖中30s~5min,并进行干燥,完成载HA/Ag/Cs涂层钛合金植入物的制备。
2.如权利要求1所述的抗感染促进成骨的钛合金植入物的制备方法,其特征在于,所述的碱热处理是指,加热状态下,采用碱处理钛合金植入物本体。
3.如权利要求2所述的抗感染促进成骨的钛合金植入物的制备方法,其特征在于,所述的碱热处理是指,水热釜中采用4M KOH, 80℃, 90min处理钛合金植入物本体。
4.如权利要求1所述的抗感染促进成骨的钛合金植入物的制备方法,其特征在于,所述的多巴胺活化是指,将钛合金植入物本体置于2mg/mL多巴胺溶液中浸泡24h。
5.如权利要求1所述的抗感染促进成骨的钛合金植入物的制备方法,其特征在于,所述的HA嫁接是指,将钛合金植入物本体浸泡1倍模拟体液中接枝HA,并置于37℃恒温箱中,每三天换一次液,浸泡14天。
6.如权利要求1所述的抗感染促进成骨的钛合金植入物的制备方法,其特征在于,采用3D打印制备钛合金植入物本体。
7.一种根据权利要求1-6中任意一项所述的制备方法制得的抗感染促进成骨的钛合金植入物,其特征在于,该植入物包含:钛合金植入物本体,及,覆盖在该钛合金植入物本体上的HA/Ag/Cs涂层。
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